Search

Background/aims: To determine the suitability of functional MRI (fMRI) as an objective measure of macular function following therapeutic intervention; conventional psychophysical measures rely heavily on patient compliance., Methods: Twenty patients with neovascular age-related macular degeneration (nAMD) were studied with high-resolution fMRI, visual acuity, reading accuracy and speed, contrast sensitivity (CS) and microperimetry (MP) before and after 3 monthly intravitreal injections of ranibizumab. Population-receptive field retinotopic maps calculated from fMRI data were compared with psychophysical measures and optical coherence tomography., Results: Best-corrected visual acuity (BCVA) responders (≥5 letters) showed an increase of 29.5% in activated brain area, while non-responders showed a decrease of 0.8%. Radial histograms over eccentricity allowed quantification of the absolute number of significant voxels and thus differences before and after treatment. Responders showed increases in foveal (α<0.5°) activation, while non-responders did not. Absence of intraretinal fluid and preservation of outer retinal layers was associated with higher numbers of active V1 voxels and better BCVA. Higher voxel numbers were associated with improved reading performance and, less marked, with BCVA, CS and MP., Conclusion: The data show that retinotopic mapping using fMRI can successfully be applied objectively to evaluate the therapeutic response in nAMD patients treated with anti-vascular endothelial growth factor therapy. This demonstrates the ability of retinotopic mapping to provide an objective assessment of functional recovery at a cortical level; the technique can therefore be applied, in other degenerative macular diseases, to the assessment of potential therapeutic interventions such as gene therapy or cell replacement therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To assess the impact of neurodegenerative morphologic alterations due to macular telangiectasia type 2 (MacTel) on microperimetry (MP) and multifocal electroretinography (mfERG)., Methods: Thirty-five eyes of 18 patients with MacTel were examined using spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), mfERG and MP. Software was used to match SD-OCT B-scans with the corresponding retinal sensitivity map and multifocal electroretinograms (mfERGs), thus enabling direct structure/function correlation., Results: Loss of the ellipsoid zone (EZ) had the strongest negative association with retinal sensitivity (16.77 dB versus 4.58 dB, adj. p < 0.001) of all parameters examined, and a limited negative effect on mfERGs (0.32 SD versus -1.97 SD adj. p = 0.121). Ellipsoid zone (EZ) irregularity was associated with reduced MP values but preserved mfERGs. There was a significant association between areas of inner retinal hyporeflectivity and loss of MP sensitivity (adj. p < 0.001) but the reduction in sensitivity was less than in locations with EZ loss. Areas of mfERG abnormality showed similar sensitivity loss with either inner retinal hyporeflectivity or EZ loss (adj. p = 0.063). In areas with EZ loss alone, preservation of the external limiting membrane (ELM) was associated with higher MP values than in areas with additional ELM loss; the integrity of the ELM alone was not associated with changes either in MP or mfERG. Increased FAF was observed in 51% of eyes, mixed/reduced FAF in 40%, and no abnormality was detected in 9% of eyes., Conclusion: The data suggest both MP and mfERG to be useful non-invasive modalities for detecting localised macular dysfunction in MacTel. The findings suggest a different sensitivity of the two modalities to inner and outer retinal changes in macular function and are therefore complementary., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The present study describes retinotopic mapping of the primary visual cortex using functional MRI (fMRI) in patients with retinal disease. It addresses the relationship between fMRI data and data obtained by conventional assessment including microperimetry (MP) and structural imaging., Methods: Initial testing involved eight patients with central retinal disease (Stargardt disease, STGD) and eight with peripheral retinal disease (retinitis pigmentosa, RP), who were examined using fMRI and MP (Nidek MP-1). All had a secure clinical diagnosis supported by electrophysiological data. fMRI used population-receptive field (pRF) mapping to provide retinotopic data that were then compared with the results of MP, optical coherence tomography and fundus autofluorescence imaging., Results: Full analysis, following assessment of fMRI data reliability criteria, was performed in five patients with STGD and seven patients with RP; unstable fixation was responsible for unreliable pRF measurements in three patients excluded from final analysis. The macular regions in patients with STGD with central visual field defects and outer retinal atrophy (ORA) at the macula correlated well with pRF coverage maps showing reduced density of activated voxels at the occipital pole. Patients with RP exhibited peripheral ORA and concentric visual field defects both on MP and pRF mapping. Anterior V1 voxels, corresponding to peripheral regions, showed no significant activation. Correspondence between MP and pRF mapping was quantified by calculating the simple matching coefficient., Conclusion: Retinotopic maps acquired by fMRI provide a valuable adjunct in the assessment of retinal dysfunction. The addition of microperimetric data to pRF maps allowed better assessment of macular function than MP alone. Unlike MP, pRF mapping provides objective data independent of psychophysical perception from the patient., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Population receptive field (pRF) mapping based on functional magnetic resonance imaging (fMRI) is an ideal method for obtaining detailed retinotopic information. One particularly promising application of pRF mapping is the estimation and quantification of visual field effects, for example scotomata in patients suffering from macular dysfunction or degeneration (MD) or hemianopic defects in patients with intracranial dysfunction. However, pRF mapping performance is influenced by a number of factors including spatial and temporal resolution, distribution of dural venous sinuses and patient performance. This study addresses the ability of current pRF methodology to assess the size of simulated scotomata in healthy individuals. The data demonstrate that central scotomata down to a radius of 2.35° (4.7° diameter) visual angle can be reliably estimated in single subjects using high spatial resolution protocols and multi-channel receive array coils., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Background: Photoreceptor damage, reported in single observations, has been suggested to contribute to the disease pathogenesis in macular telangiectasia type 2 (MacTel2). The purpose of this study was to ascertain whether the photoreceptor or post-photoreceptoral function is affected in MacTel2 and could be detected using electrophysiological examination., Methods: Thirty-five eyes from 18 patients (15 men, aged 60.1±9.6 years, range 38-77 years) with MacTel2 were included in the study. All patients underwent standard ophthalmic examination followed by pattern electroretinography (PERG) and full-field ERG. The data were compared against 22 normal control subjects (10 men, age 59.83±6.28 years, range 48-76)., Results: Mean PERG P50 amplitude and peak time in patients with MacTel2 did not differ significantly from control values (p>0.2) but P50 amplitude was subnormal in three patients. The mean scotopic rod b-wave amplitude was significantly lower in patients than in healthy controls (p=0.027). A lower dark-adapted 10.0 b-wave (p=0.06) but not a-wave amplitude (p=0.58) was present in patients with MacTel2. Photopic single-flash a-wave and b-wave amplitudes did not differ between patient and control groups (p=0.2 and 0.3), but 30 Hz flicker peak time was significantly later in patients with MacTel2 with no effect on amplitude (p=0.04 and 0.7)., Conclusion: Both scotopic (rod system dominated) and photopic ERGs (cone system) are consistent with post-photoreceptoral dysfunction. There was no electrophysiological evidence of dysfunction at the level of the photoreceptor., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To improve structure-function analysis in primary open-angle glaucoma (POAG) by including the two-global flash multifocal electroretinogram (2F-mfERG) and macular ganglion cell layer segmentation., Methods: Twenty-five glaucoma patients (six pre-perimetric (PPG), 19 POAG) and 16 controls underwent 2F-mfERG, optical coherence tomography (OCT), and standard automated perimetry (SAP). For 2F-mfERG, the root mean square was calculated for the focal flash response at 15-45 ms (DC) and the global flash responses at 45-75 ms (IC1) and 75-105 ms (IC2). For OCT, macular total thickness (mT) and ganglion cell-inner plexiform layer (GCIPL) thickness were analysed. Values from the central 10° and 15° of 2F-mfERG were compared to the corresponding areas from OCT and visual field., Results: Both PPG and POAG had significantly lower mfERG responses in the central 10° and 15° than the control group. Of the glaucoma patients, 30.7% (three PPG, five POAG) showed central mfERG and GCIPL reduction without a SAP defect in the central 15 degrees. Four patients had a central SAP defect associated with a reduced GCIPL without any detectable dysfunction on mfERG. MfERG DC and IC2 were larger with increased mT (p ≤ 0.02), but GCIPL only related positively to IC2 (p = 0.027). SAP sensitivity also increased with thicker mT but not with GCIPL (p < 0.03 and p = 0.35). DC, IC2, and GCIPL could best differentiate glaucoma from control (AUC values: 0.897, 0.903, and 0.905)., Conclusions: Structure function analysis in glaucoma can be improved when the GCIPL thickness as well as the 2F-mfERG is included as these measures complement information obtained by SAP.

Purpose: To further improve analysis of the two-flash multifocal electroretinogram (2F-mfERG) in glaucoma in regard to structure-function analysis, using discrete wavelet transform (DWT) analysis., Methods: Sixty subjects [35 controls and 25 primary open-angle glaucoma (POAG)] underwent 2F-mfERG. Responses were analyzed with the DWT. The DWT level that could best separate POAG from controls was compared to the root-mean-square (RMS) calculations previously used in the analysis of the 2F-mfERG. In a subgroup analysis, structure-function correlation was assessed between DWT, optical coherence tomography and automated perimetry (mf103 customized pattern) for the central 15°., Results: Frequency level 4 of the wavelet variance analysis (144 Hz, WVA-144) was most sensitive (p < 0.003). It correlated positively with RMS but had a better AUC. Positive relations were found between visual field, WVA-144 and GCIPL thickness. The highest predictive factor for glaucoma diagnostic was seen in the GCIPL, but this improved further by adding the mean sensitivity and WVA-144., Conclusions: mfERG using WVA analysis improves glaucoma diagnosis, especially when combined with GCIPL and MS.

Purpose: To validate a new automated perimetry pattern (mf103 pattern) for the investigation of retinal structure-function relationships in glaucoma in comparison to the standard G2 pattern and to relate either field's performance to optical coherence tomography (OCT)., Methods: Automated perimetry data from the mfERG103 pattern were compared with the standard G2 pattern in glaucoma patients (18) and controls (15). The results of both (mean defect (MD) and mean sensitivity (MS)) were compared with optical coherence tomography (OCT): retinal nerve fiber layer (RNFL) thickness, macular thickness (mT), and ganglion cell analysis (GCIPL). Nine patients were followed up after one year., Results: G2 pattern and mf103 pattern did not differ significantly in MD or MS. The mf103 pattern associated significantly with more RNFL sectors in both MD and MS ( p < 0.01 and p < 0.05, resp.). GCIPL thickness was not significantly associated with either SAP protocols. Both protocols remained comparable after one-year follow-up., Conclusions: G2 and mf103 pattern can both differentiate patients from controls with no significant difference in performance. RNFL thickness defects correlated better with mf103 than G2 with POAG. The mfERG-103 perimetry pattern can be used to establish structure-function correlations in glaucoma and may enable a more direct comparison with objective electrophysiological data.

Functional MRI enables the acquisition of a retinotopic map that relates regions of the visual field to neural populations in the visual cortex. During such a "population receptive field" (PRF) experiment, stable gaze fixation is of utmost importance in order to correctly link the presented stimulus patterns to stimulated retinal regions and the resulting Blood Oxygen Level Dependent (BOLD) response of the appropriate region within the visual cortex. A method is described that compensates for unstable gaze fixation by recording gaze position via an eyetracker and subsequently modifies the input stimulus underlying the PRF analysis according to the eyetracking measures. Here we show that PRF maps greatly improve when the method is applied to data acquired with either saccadic or smooth eye movements. We conclude that the technique presented herein is useful for studies involving subjects with unstable gaze fixation, particularly elderly patient populations., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Purpose. To compare two different spectral-domain optical coherence tomography (OCT) systems in regard to full macular thickness (MT) and ganglion cell layer-inner plexiform layer (GCIPL) measures and in regard to structure-function correlation when compared to standard automated perimetry (SAP). Methods. Seventeen primary open angle glaucoma patients and 16 controls (one eye per subject) were enrolled. MT and GCIPL thicknesses were measured by Cirrus and Spectralis OCTs. Octopus Perimeter 101 (G2 protocol) reports sensitivity in mean defect (dB). Differences between measurements were assessed with Student's t-test and Bland Altman. Diagnostic performance was also compared between each parameter calculating the areas under the operator receiver (ROC). Linear models were used to investigate structure-function association between OCT and SAP. Results. Disagreement between OCTs in both MT and GCIPL values was significant. Spectralis values were thicker than Cirrus. Average difference between OCTs was 21.64 μm (SD 4.5) for MT and 9.8 μm (SD 5.4) for GCIPL (p < 0.001). Patients differed significantly from controls in both OCTs, in both measurements. MT and GCIPL were negatively associated with MD (p < 0.001). Conclusions. Although OCT values were not interchangeable, both machines differentiated patients from controls with statistical significance. Structure-function analysis results were comparable, when either OCT was compared to SAP.

Purpose: To assess the effect of a 50 Hz power line digital filter on the response to a 2-global-flash multifocal electroretinogram (mfERG) in primary open angle glaucoma (POAG) compared to control., Materials and Methods: A 2-global-flash mfERG (VERIS™) was recorded (23 control, 34 POAG). Eight recordings were noise contaminated: 4 control, 4 POAG. Response averages from the central 10° and 7 surrounding groups were analyzed with and without a 50 Hz digital filter for the following mfERG response epochs: direct component (15-45 ms), 1st (45-75 ms) and 2nd (75-105 ms) induced components., Results: A digital 50 Hz filter had little effect on uncontaminated with noise waveforms but, in noisy recordings, changed the waveform dramatically to resemble uncontaminated waveforms. In controls' 50 Hz-filtered uncontaminated with noise mfERGs differed significantly from unfiltered responses in induced components. Uncontaminated with noise recordings from glaucoma patients did not differ with or without the notch filter (p > 0.1 for all three epochs of mfERG). The mfERG response in the central 10°in glaucoma patients differed significantly from controls, whether the notch filter was used or not (p < 0.001)., Conclusions: A 50 Hz notch filter allows grossly contaminated waveforms to be analyzed in a meaningful manner. With a 50 Hz filter, glaucoma patients still differed significantly from normal.

Purpose: To correlate multifocal electroretinogram (mfERG) findings in the macular area of glaucoma patients with automated perimetry (visual fields) and with optical coherence tomography (OCT)., Methods: A two-global flash mfERG (VERIS™) was recorded in 20 eyes with primary open-angle glaucoma. The root mean square was calculated, and three response epochs were analysed: the direct component (15-45 ms) and two induced components (IC-1 at 45-75 ms and IC-2 at 75-105 ms). The central 10° of the mfERG was compared to the central 10° of the OCT and of the visual field. Responses grouped in a superior and in an inferior semicircle, extending between 10° and 20°, were also compared to the corresponding areas of the OCT and of the visual fields. In addition, the area of the papillomacular bundle was also analysed separately., Results: In glaucoma patients, mfERG responses showed a significant positive association with retinal thickness in the central 10° for IC2 (p = 0.001) and a trend for IC1 (p = 0.066). A significant association was found between the central IC1 and IC2 of the mfERG and corresponding perimetric sensitivities expressed in linear units (p < 0.01). The OCT showed a positive association with visual field sensitivities (p < 0.05) in all areas examined (p < 0.05). Separation of the papillomacular bundle area did not improve structure-function association further., Conclusions: In our study, mfERG showed a statistically significant correlation with perimetric sensitivity measured in linear units and with structural macular changes detected with time-domain OCT.

Purpose: To study the effects of filtering bandwidth on the two-global-flash multifocal electroretinogram (mfERG) responses in primary open-angle glaucoma (POAG) compared with control subjects., Methods: A two-global-flash mfERG (VERIS 6.06™, FMS III) was recorded in 20 healthy subjects and 22 POAG patients with a band-pass filter (BPF) of 1-300 Hz (103 Hexagons, M-sequence stimulus: Lmax 100 cd/m(2), Lmin < 1 cd/m(2), global flash: 200 cd/m(2)). The root-mean-square average of the central 10° was calculated. Three response epochs were analysed: the response to the focal flash, at 15-45 ms (DC), and the following two components induced by the effects of the preceding focal flash on the response to the global flashes at 45-75 ms (IC1) and at 75-105 ms (IC2). The following BPF settings were analysed: 1-300 Hz, 3-300 Hz, 10-300 Hz, 100-300 Hz, 200-300 Hz, 1-10 Hz, 1-100 Hz and 1-200 Hz., Results: Filtering at 1-300 Hz showed significantly lower responses in POAG than in control subjects (p < 0.001) for all epochs analysed. At 1-100 Hz, this also held true even though the difference between the groups became smaller. At 1-10 Hz, responses were extremely small and did not differ between POAG and control (p > 0.5). This would suggest a filter setting of 10-300 Hz for mfERG recordings in POAG. However, when a filter setting of 10-300 Hz was compared to 1-300 Hz, with a filter setting of 10-300 Hz, the DC in POAG differed more (p < 0.0001) from normal than with 1-300 Hz (p = 0.0002). For IC1 and IC2, the stronger difference between POAG and control was found with 1-300 Hz (p < 0.0001) rather than with 10-300 Hz (p < 0.0001 and p = 0.0005, respectively). For the 'oscillatory potentials' at 100-300 Hz, POAG and control differed significantly in IC1 and IC2 (p < 0.05), but not in DC (p = 0.8). However, filtering at 200-300 Hz did not show a difference between POAG and control (p > 0.5). Thus, we applied a filter setting of 1-200 Hz, which seemed to be most sensitive in detecting glaucomatous retinal dysfunction (p < 0.0001)., Conclusions: A filter setting of 1-200 Hz appears most sensitive to detect glaucomatous damage if using a two-global-flash mfERG: using a band-pass filter a with lower low-frequency cut-off, containing the 10 Hz component, may be especially important in the small induced components that show glaucomatous damage most sensitively. High frequencies of 100-300 Hz also contain information that differentiates glaucoma from normal and thus should be included in the analysis.

Purpose: To test a new 2-flash multifocal electroretinogram (mfERG) paradigm in glaucoma using a reduced light intensity of the m-frame flash as opposed to the global flash, as it has been suggested that this may increase the responses induced by the global flash, which has been the part of the mfERG response where most changes have been noted in glaucoma., Methods: A mfERG was recorded from one eye of 22 primary open angle glaucoma (POAG) patients [16 normal tension glaucoma (NTG), 6 high tension glaucoma (HTG)] and 20 control subjects. A binary m-sequence (2^13-1, Lmax 100 cd/m2, Lmin<1 cd/m2), followed by two global flashes (Lmax 200 cd/m2) at an interval of 26 ms (VERIS 6.0™, FMSIII), was used. The stimulus array consisted of 103 hexagons. Retinal signals were amplified (gain=50 K) and bandpass filtered at 1-300 Hz. For each focal response, the root mean square was calculated. We analyzed 5 larger response averages (central 15° and 4 adjoining quadrants) as well as 8 smaller response averages (central 10° and 7 surrounding response averages of approximately 7° radius each). Three epochs were analyzed: the direct component at 15-45 ms (DC) and the following two components induced by the effects of the preceding focal flash on the response to the global flashes at 45-75 ms (IC-1) and at 75-105 ms (IC-2). Statistical analysis was performed using linear mixed effects models adjusted for age., Results: Responses differed significantly between POAG patients and controls in all central response averages. This difference was larger for the central 10° than for the response average of the central 15°. While these observations held true for all response epochs analyzed, the DC differed least and the IC-1 most when POAG was compared to control. For POAG, the most sensitive differential measure was IC-1 of the central 10° with an area under the ROC curve of 0.78. With a cutoff value of 12.52 nV/deg2, 80% of the POAG patients (100% HTG, 69% NTG) were correctly classified as abnormal, while 77% of the control subjects were correctly classified as normal. When the results of the mfERG were compared to the visual fields, there was a tendency for the mfERG to decrease as the mean defect increased. However, this correlation was only significant in the superior nasal quadrant when the IC-1 of the mfERG was compared to the corresponding area of the visual field., Conclusion: When compared to findings from previous studies, reducing the luminance of the m-frame flash in the 2-global flash paradigm did not increase the sensitivity and specificity of the mfERG to detect glaucoma further.